Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed.
| Authors | |
| Abstract | Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( = 6454) and lung ( = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation. |
| Year of Publication | 2026
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| Journal | Science (New York, N.Y.)
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| Volume | 393
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| Issue | 6808
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| Pages | eadx2989
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| Date Published | 07/2026
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| ISSN | 1095-9203
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| DOI | 10.1126/science.adx2989
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| PubMed ID | 42462027
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